It is well known that many drugs if taken orally, are destroyed on the first past through the liver. It is also well known that when many drugs are taken orally, their rate of absorption into the body is not constant. In view of such difficulties, a number of different drug delivery systems have been developed. Recently, the use of transdermal delivery systems have met with increasing interest by researchers in the pharmaceutical drug delivery field.
U.S. Pat. No. 4,291,015 to Keith, et al. discloses the use of a polymeric diffusion matrix for the sustained release of pharmaceutically active drugs. The matrix is covered by a backing layer and applied to the skin where diffusion of the pharmaceutically active drug occurs and the drug is transdermally delivered to the patient. Although U.S. Pat. No. 4,291,015 discloses transdermal delivery of nitroglycerin, other drugs may be delivered by utilizing the same or a similar matrix, as disclosed in U.S. Pat. Nos. 4,294,820; 4,292,302; and 4,292,303.
U.S. Pat. No. 4,409,206 discloses the use of a different type of transdermal delivery system whereby the pharmaceutically active drug is dispersed within an adhesive (see also U.S. Pat. No. 4,390,520). In accordance with such systems, the pharmaceutically active drug is dispersed in a pressure-sensitive adhesive which is adhered to the skin. The drug then diffuses from the adhesive through the skin for delivery to the patient.
Other transdermal systems involve the use of a matrix which is in diffusional contact with a reservoir which contains the pharmaceutically active drug. The drug diffuses to the matrix and then to the skin and eventually to the patient. Still other compositions include an active ingredient in a salve or ointment which is applied to skin. The active ingredient diffuses from the salve to the skin and enters the body transdermally.
Each of the systems have various advantages and disadvantages with respect to the transdermally delivery of pharmaceutically active drugs. Certain systems may be useful in connection with one type of pharmaceutically active drug and not useful in connection with another. The ability to include one pharmaceutically active drug within a given system depends on various factors such as the compatibility of the drug with the system and the effects of the drugs on the system such as its ability to dissolve in the system. Without experimentation, it is often impossible to accurately predict the usefulness of any particular system with any particular pharmaceutically active drug. However, the present inventor has found that all the systems do have certain similarities and more importantly a common undesirable feature. More specifically, they all operate by transporting the pharmaceutically active drug to the skin for transdermal delivery. In order to accomplish this, the system must be placed in intimate contact with the skin. Since normal skin will perspire such will create an aqueous layer between the skin and the system. It is this aqueous layer which causes the common disadvantage.
Perspiration may well be increased beneath a transdermal delivery system and any perspiration beneath a delivery system causes an outflow of water and other water soluble body salts from the skin. This increased outflow increases the size of the aqueous layer and thus hinders the desired inflow of the pharmaceutically active drug through the skin. When the system remains in place for a substantial period of time (24 hours is common), the outflow of perspiration can build up a substantial aqueous layer between the delivery system and the skin. This impediment is especially great if the pharmaceutically active drug is insoluble with respect to the aqueous layer or if the drug is in any way incompatible with the aqueous layer or coagulates upon contact with it. The present invention is directed to elimination of the undesirable outflow of perspiration from the skin and the undesirable accumulation of that perspiration (aqueous layer formation) between the skin and the drug delivery system.